Cohort profile: the Entebbe Mother and Baby Study (EMaBS).

Abstract

The Entebbe Mother and Baby Study (EMaBS) was established in 2001 to test the hypothesis that treating helminth infections during pregnancy and early childhood could improve children's responses to Bacillus Calmette-Guérin (BCG) and other vaccines given in infancy and influence immune responses to other infectious pathogens. Follow-up was subsequently extended to address further research questions and continue to the present day. Two thousand five hundred and seven pregnant women were recruited when attending antenatal services at Entebbe General Hospital, Uganda; 2345 resulting live-born children were enrolled into the EMaBS birth cohort. Initial results from EMaBS showed that treating helminths in pregnancy and early childhood was safe and that treatment with albendazole reduced anaemia in mothers with heavy hookworm infections. Maternal anthelminthic treatment had small effects on infant response to tetanus immunisation, but no effect, either beneficial or detrimental on the occurrence of infectious diseases in childhood. However, treatment of helminths during pregnancy resulted in increased rates of eczema in early childhood, although this was not sustained to nine years. Subsequent work in early adolescence found that postnatal weight gain was important in the developmental programming of blood pressure in this population and current and early-life malaria modified blood pressure and lipid levels. We also showed that variation in host genes significantly shapes antibody responses to multiple childhood vaccines, highlighting genetics as a key determinant of vaccine performance. Cohort 'children' are currently aged 19-22 years, and future plans focus on investigating longer term effects of early-life and childhood exposures. A new round of data collection is ongoing with the aim of determining the impact of early-life exposures on adult non-communicable disease risk. Work determining whether frequent childhood infections lead to specific epigenetic changes implicated in later disease development is also underway. The EMaBS began as a randomised controlled trial (ISRCTN32849447). Two further randomised controlled trials have been nested within the cohort: TB042 (NCT03681860) and POPVAC C (ISRCTN10482904).